Modification of the L1-CAM carboxy-terminus in pancreatic adenocarcinoma cells

The neural cell adhesion molecule L1 has recently been shown to be expressed in pancreatic adenocarcinoma (PDAC) cells. In this report, we demonstrate that L1 is expressed by moderately- to poorly-differentiated PDAC cells in situ, and that L1 expression is a predictor of poor patient survival. In vitro, reduced reactivity of an anti-L1 carboxy-terminus-specific antibody was observed in the more poorly differentiated fast-growing (FG) variant of the COLO357 population, versus its well-differentiated slow-growing (SG) counterpart, even though they express equivalent total L1. The carboxy-terminus of L1 mediates binding to the MAP kinase-regulating protein RanBPM and mutation of T1247/S1248 within this region attenuates the expression of malignancy associated proteins and L1-induced tumorigenicity in mice. Therefore, we reasoned that the differential epitope exposure observed might be indicative of modifications responsible for regulating these events. However, epitope mapping demonstrated that the major determinant of binding was actually N1251; mutation of T1247 and S1248, alone or together, had little effect on C20 binding. Moreover, cluster assays using CD25 ectodomain/L1 cytoplasmic domain chimeras demonstrated the N1251-dependent, RanBPM-independent stimulation of erk phosphorylation in these cells. Reactivity of this antibody also reflects the differential exposure of extracellular epitopes in these COLO357 sublines, consistent with the previous demonstration of L1 ectodomain conformation modulation by intracellular modifications. These data further support a central role for L1 in PDAC, and define a specific role for carboxy-terminal residues including N1251 in the regulation of L1 activity in PDAC cells

Cystic lymphangioma of the lesser curvature of the stomach - case report

We report a case of a cystic lymphangioma arising from the lesser curvature of the stomach in a 16-year-old female who initially presented with abdominal pain, nausea, and emesis. Contrast enhanced computed tomography and magnetic resonance imaging revealed a large, thin-walled multicystic mass located anteromedial to the stomach, which was predominately supplied by the left gastric artery. Given the imaging appearance and location, a mesenteric cyst, specifically a cystic lymphangioma, was considered. Lymphangioma was the final pathological diagnosis after laparotomy with complete resection of the cystic abdominal mass

New Disposable Transanal Endoscopic Surgery Platform: Longer Channel, Longer Reach

Abstract: Background: Transanal endoscopic surgical (TES) resection using rigid transanal platforms (TEM, TEO) is associated with improved outcomes compared to traditional transanal excision (TAE) of rectal lesions. An alternative technique using a disposable single incision surgery platform was developed in 2009, transanal minimally invasive surgery (TAMIS), resulting in a surge in interest and access to transanal access platforms to perform TES. However, compared to rigid transanal access platforms, the disposable platforms do not facilitate internal rectal retraction and have limited proximal reach. A new long channel disposable transanal access platform has been developed (15 cm in length, 4 cm in width) thereby facilitating endoluminal surgical access to the upper rectum and rectosigmoid colon. Methods: This is a retrospective case series report. Patient demographics and peri-operative outcome variables were recorded. The Gelpoint Path Long Channel was utilized in three patients with proximal rectal lesions that were not accessible using a standard disposable transanal access platform.Results: Three patients underwent TES excision of rectal adenomas using a long channel, disposable, transanal access platform. All patients were female, aged 51 – 53, BMI 23-32 kg/m2. The tumor size ranged from 2.4 – 8.5 cm, 15-100% circumference, and proximal location from the dentate line ranged from 9 – 11 cm. Final pathology revealed adenoma with negative margins in all three cases. The hospital length of stay ranged from 1 – 3 days and there were no perioperative complications. None of the patients have developed a local recurrence during the follow up period ranging from 5 – 11 months.Conclusions: The new long channel, disposable, transanal access platform facilitates transanal endoluminal surgical removal of lesions in the mid to upper rectum that may be difficult to reach using the standard disposable transanal access devices. We have successfully achieved 100% margin negative rate using this new device in this small series of patients with proximal rectal adenomas

Redefining the Anatomic Boundaries for Safe Dissection of the Skin Paddle in a Gracilis Myofasciocutaneous Free Flap: An Indocyanine Green Cadaveric Injection Study

Summary:. The gracilis free flap remains a versatile option in the reconstructive ladder. The flap itself can be harvested with or without a skin paddle. The gracilis myocutaneous free flap, however, is known for partial skin flap necrosis, especially in the distal one-third of the skin island. The gracilis myofasciocutaneous flap has been previously described as a technique to improve perfusion to the skin by harvesting surrounding deep fascia in a pedicled flap. However, limitations to this study required injection of multiple pedicles to demonstrate its perfusion. We demonstrate a novel technique using a cadaveric model that shows perfusion through injection via a single dominant pedicle (medial circumflex) with a large cutaneous paddle (average 770 cm2) with included deep fascia, using indocyanine green and near-infrared imaging. For comparison, we are also able to confirm the lack of perfusion to the distal cutaneous paddle when the fascia is not harvested, correlating with previous findings and ink injection studies. This novel technique is versatile, relatively inexpensive, and can demonstrate perfusion patterns via perforasomes that were otherwise not possible from previous techniques. Additionally, real-time imaging is possible, helping to elucidate the sequence of flow into the flap and potentially predict areas of flap necrosis

Transanal Endoscopic Surgical Proctectomy for Proctitis Case Series Report: Diversion, Radiation, Ulcerative Colitis, and Crohn’s Disease

Abstract: Background: With recent trends in natural orifice surgery, there has been a rising interest in the evolution of transanal endoscopic surgery (TES) and transanal access platforms. Transanal endoluminal removal of rectal masses has matured into transanal endoscopic surgical resection of the rectum for benign and malignant disease. The purpose of this study is to evaluate the surgical outcomes of TES completion proctectomy in patients with proctitis in a retained rectum.Methods: This is a retrospective case series report. Patient demographics and peri-operative outcome variables were recorded.Results: TES proctectomy was successfully performed in 6 patients using a disposable transanal access platform. The patient's ages ranged from 22 – 74 years, 4 women and 2 men, BMI ranged from 22 – 51 kg/m2. The indication for surgery was proctitis in a retained rectum: diversion (n=1), radiation (n=1), ulcerative colitis (n=2), and Crohn's disease (n=2). Four applications of TES proctectomy were employed: TES completion proctectomy (n=2), TES assisted single incision abdominal perineal resection (n=1), TES assisted laparoscopic restorative proctectomy with colo-anal anastomosis (n=1), and TES assisted laparoscopic restorative total proctocolectomy with ileal pouch anal anastomosis (n=1). The operative time for TES completion proctectomy ranged from 140 – 238 minutes (n=4). The operative time for TES restorative proctectomy was longer at 446 min and 557 min (n=2). The hospital length of stay for both TES completion and restorative proctectomy ranged from 2 – 5 days (n=5). Complications included 1 urinary tract infection, 1 chronic draining perineal sinus tract, and 1 perineal wound dehiscence requiring re-operation. All six patients are doing well at the time of follow up (range 3 – 19 months).Conclusions: TES completion proctectomy alone or in combination with laparoscopic abdominal surgery is a safe and effective method to perform proctectomy and restorative proctectomy in this small case series of patients with proctitis in a retained rectum due to diversion, radiation, ulcerative colitis, and Crohn's disease

Inside-Out Regulation of L1 Conformation, Integrin Binding, Proteolysis, and Concomitant Cell Migration

The ectodomain structure and function of the neural cell adhesion molecule L1 is shown to be regulated by the intracellular phosphorylation of a novel threonine, T1172. In pancreatic cancer cells, T1172 exhibits steady-state saturated phosphorylation, an event regulated by CKII and PKC, and which further regulates cell migration